TETRANECTIN - A PLASMINOGEN BINDING PROTEIN. I. Kjøller Larsen, B. B. Nielsen, H. Rasmussen, J. S. Kastrup, Dept. of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark

Tetranectin (TN) is a plasma protein, which binds specifically to the kringle 4 (K4) domain of plasminogen (1). The fibrinolytic proteins of the plasminogen activator/plasmin system are known to be involved in extracellular proteolysis, and is believed to be involved in the spread of cancer by invasion and metastasis. The concentration of TN is increased in cells with high metabolic activity, and is present in the extracellular matrix during tissue remodelling in contrast to normal tissues (2).

TN is a trimeric protein with three identical polypeptide chains each of 181 amino acid residues. TN has been shown to consist of three domains: TN1 (residues 1-16), TN2 (residues 17-49), which is the K4 binding domain, and TN3 (residues 50-181). Sequence identity has been found between TN3 and other proteins containing a Ca²⁺ dependent C- type lectin domain, e.g. the mannose binding protein (MBP). TN and the individual domains, as well as combinations of domains, have been expressed in E. coli (3), and X-ray structure determinations are in progress.

The structure of TN3 (2.7 Å resolution) has been solved by the MR method using the C-lectin domain of MBP as search model. A full data set of TN has been collected to 3.5 Å resolution, and an MR solution has been obtained, also with MBP as search model. TN exists in the crystal as a trimer in contrast to TN3, which is a monomer both in crystal and in solution. Crystals diffracting to 7 Å have been obtained of TN2,3.

1. Clemmensen, I., Petersen, L. C. & Kluft, C. (1986) Eur. J. Biochem 156, 327-333

2. Høgdall, C. K, Christensen, L. & Clemmensen, I. (1993) Cancer 72, 2415-2422

3. Holtet, T. L, Etzerodt, M. & Thøgersen, H. C. Laboratory of Gene Expression, Århus University, Gustav Wieds vej 10, DK-8000 Århus, Denmark. To be published